K. Richter

Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium

Mesenchymal stem cells have been shown to mediate immunomodulatory effects. They have been used in patients with steroid-refractory acute GVHD (aGVHD), but their relevance as a therapeutic agent targeting aGVHD has still to be defined. In this case series, we report 13 patients with steroid-refractory aGVHD who received BM-derived MSC expanded in platelet lysate-containing medium from unrelated HLA disparate donors. MSC were characterized by their morphological, phenotypical and functional properties. All tested preparations suppressed the proliferation of in vitro activated CD4+ T cells. MSC were transfused at a median dosage of 0.9 × 106/kg (range 0.6–1.1). The median number of MSC applications was 2 (range 1–5). Only two patients (15%) responded and did not require any further escalation of immunosuppressive therapy. Eleven patients received additional salvage immunosuppressive therapy concomitant to further MSC transfusions, and after 28 days, five of them (45%) showed a response. Four patients (31%) are alive after a median follow-up of 257 days, including one patient who initially responded to MSC treatment. In our patient cohort, response to MSC transfusion was lower than in the series reported earlier. However, our experience supports the potential efficacy of MSC in the treatment of steroid-refractory aGVHD.

Wide field-of-view all-reflective objectives designed for multispectral image acquisition in photogrammetric applications

In many aerial and close-range photogrammetry applications, the near infrared (NIR) spectral range is required in addition to the visible (VIS) spectral range. Currently, many especially aerial photogrammetric systems use particularly optimized camera systems for each spectral band. Using separate cameras or lenses can introduce parallaxes and timedelays between the acquired images, and thus complicate the data fusion process. Furthermore, it adds additional weight to the entire system. With an image acquisition through a single objective, the complexity of the data fusion and the weight can be significantly reduced. However, to be able to only use one objective for different spectral bands, the optical system has to be free of chromatic aberrations. For photogrammetric applications, a wide field-of-view and a high resolution are frequent additional requirements. Therefore, we will present a design and an adapted photogrammetric calibration method of an all-reflective unobscured optical system optimized for full-frame imaging sensors. All-reflective unobscured optical systems may also be a very efficient imaging tool in combination with unmanned aerial vehicles (UAVs). Due to the limited payload capacity, many currently available UAVs can only be used with one spectrally limited camera system at the same time. With miniaturized all-reflective camera systems, the image data could be acquired in the visible and e.g. the NIR spectral range simultaneously.

An Approach to Determining Turbidity and Correcting for Signal Attenuation in Airborne Lidar Bathymetry

Airborne lidar bathymetry is an efficient technique for measuring the bottom of shallow water bodies. A characteristical feature of lidar bathymetry beam propagation is given by scattering and absorption effects in the water column, both leading to a loss of received signal intensity. This loss of signal intensity depends on the turbidity of the water body. Inversely, an analysis of the decay of the recorded waveform signal allows for deriving statements on the local degree of turbidity in the water. The paper shows a first approach on the determination of one turbidity measure per laser pulse by analysing the recorded waveform and fitting an exponential function, wherein the decay coefficient depicts an integral measure describing turbidity. The technique was applied to a shallow inland water, and the results were validated by conventional point-wise turbidity measurement techniques. An obvious consequence of attenuation and loss of signal intensity in lidar bathymetry is the fact that the bottom returns become rather weak. In many cases, conventional ground pulse echo detection techniques fail in detecting water bottom points, leading to a reduced number of water body bottom points and thus limiting the application range of the technique. To partly compensate for this effect, a differential backscatter cross section determination based signal attenuation correction method has been developed, which allows for a signal-derived re-amplification of the ground signal. Although the technique also amplifies noise, it could be shown that it is capable of delivering a higher number of additional ground points and thus extending the applicability of the technique.

VACCINATION OF HORMONE-REFRACTORY PROSTATE CANCER PATIENTS WITH PEPTIDE COCKTAIL-LOADED DENDRITIC CELLS: RESULTS OF A PHASE I CLINICAL TRIAL

2551 Background: For patients with hormone-refractory prostate cancer (HRPC) treatment options are limited. Immunotherapies based on dendritic cells (DCs) might represent promising alternatives. In a Phase I clinical trial, we evaluated the safety and feasibility of a vaccination with monocyte-derived DCs loaded with a cocktail consisting of HLA-A*0201-restricted peptides derived from prostate cancer-associated antigens (PSA, PSMA, survivin, prostein, trp-p8). METHODS Eight HRPC patients were enrolled in this study (Table). Each patient underwent two leukaphereses, for the isolation of monocytes and subsequent generation of mature DCs. Patients received a total of four vaccinations each with peptide cocktail-loaded DCs at a dose of 1 x 107 cells both intradermally and intravenously every other week. Clinical response was monitored by the determination of the PSA level. The induction of a peptide-specific T-cell response was assessed by ELISPOT analysis. RESULTS Apart from local erythema and edema at the site of intradermal administration no side effects were noted. Four of eight patients showed a temporary PSA decline. One patient displayed a partial response with a PSA decrease > 50% for seven weeks and further stabilization for five weeks. Stable PSA values or decelerated PSA increases were observed in the three remaining patients. In ELISPOT analyses, three of four PSA responders also showed antigen-specific CD8+ T-cell activation against prostein, survivin and PSMA. CONCLUSIONS The described protocol represents a safe and feasible concept for the induction of clinical and immunological responses. The application of a peptide cocktail derived from different antigens as a novel treatment modality is supposed to allow for the genetic and biologic heterogeneity of PCa. [Table: see text] [Table: see text].

78 Identification of an HLA-A∗0201-restricted T cell epitope derived from the prostate cancer-associated protein TRP-P8

BACKGROUND New concepts for the immunotherapy of prostate carcinoma (PCa) largely depend on the identification of suitable target antigens that are present in a high percentage of prostate tumors. Their expression in normal tissues should be restricted to the prostate and they should be immunogenic in vivo. The number of antigens displaying these properties is still limited. Here, we identify for the first time an immunogenic peptide derived from the prostate-specific protein transient receptor potential-p8 (trp-p8) that is recognized by cytotoxic T lymphocytes (CTLs) from PCa patients. METHODS To determine the abundance of trp-p8 in prostate tumors, the expression level of trp-p8 mRNA was quantitatively analyzed in a panel of prostate cancer tissues. Trp-p8-derived human leukocyte antigen (HLA)-A*0201-restricted peptides were selected and tested for the in vitro activation of CTLs when loaded on autologous dendritic cells (DCs). RESULTS Trp-p8 mRNA was found to be expressed in all prostate tumors and in the corresponding normal prostate tissue. Of five selected trp-p8-derived peptides, only peptide GLMKYIGEV was shown to activate specific CTLs, which effectively lysed PCa cells confirming the endogenous generation and presentation of this peptide by tumor cells. CONCLUSIONS Our results suggest this antigen as a suitable target for the T-cell-based immunotherapy of PCa.